Tag: statistics

BMC Med Res Methodol. 2022 Aug 12;22(1):222. doi: 10.1186/s12874-022-01699-2.

ABSTRACT

BACKGROUND: Cluster randomised trials (CRTs) are often designed with a small number of clusters, but it is not clear which analysis methods are optimal when the outcome is binary. This simulation study aimed to determine (i) whether cluster-level analysis (CL), generalised linear mixed models (GLMM), and generalised estimating equations with sandwich variance (GEE) approaches maintain acceptable type-one error including the impact of non-normality of cluster effects and low prevalence, and if so (ii) which methods have the greatest power. We simulated CRTs with 8-30 clusters, altering the cluster-size, outcome prevalence, intracluster correlation coefficient, and cluster effect distribution. We analysed each dataset with weighted and unweighted CL; GLMM with adaptive quadrature and restricted pseudolikelihood; GEE with Kauermann-and-Carroll and Fay-and-Graubard sandwich variance using independent and exchangeable working correlation matrices. P-values were from a t-distribution with degrees of freedom (DoF) as clusters minus cluster-level parameters; GLMM pseudolikelihood also used Satterthwaite and Kenward-Roger DoF.

RESULTS: Unweighted CL, GLMM pseudolikelihood, and Fay-and-Graubard GEE with independent or exchangeable working correlation matrix controlled type-one error in > 97% scenarios with clusters minus parameters DoF. Cluster-effect distribution and prevalence of outcome did not usually affect analysis method performance. GEE had the least power. With 20-30 clusters, GLMM had greater power than CL with varying cluster-size but similar power otherwise; with fewer clusters, GLMM had lower power with common cluster-size, similar power with medium variation, and greater power with large variation in cluster-size.

CONCLUSION: We recommend that CRTs with ≤ 30 clusters and a binary outcome use an unweighted CL or restricted pseudolikelihood GLMM both with DoF clusters minus cluster-level parameters.

PMID:35962318 | DOI:10.1186/s12874-022-01699-2

BMC Bioinformatics. 2022 Aug 12;23(1):333. doi: 10.1186/s12859-022-04885-7.

ABSTRACT

BACKGROUND: Influenza A viruses (IAV) exhibit vast genetic mutability and have great zoonotic potential to infect avian and mammalian hosts and are known to be responsible for a number of pandemics. A key computational issue in influenza prevention and control is the identification of molecular signatures with cross-species transmission potential. We propose an adjusted entropy-based host-specific signature identification method that uses a similarity coefficient to incorporate the amino acid substitution information and improve the identification performance. Mutations in the polymerase genes (e.g., PB2) are known to play a major role in avian influenza virus adaptation to mammalian hosts. We thus focus on the analysis of PB2 protein sequences and identify host specific PB2 amino acid signatures.

RESULTS: Validation with a set of H5N1 PB2 sequences from 1996 to 2006 results in adjusted entropy having a 40% false negative discovery rate compared to a 60% false negative rate using unadjusted entropy. Simulations across different levels of sequence divergence show a false negative rate of no higher than 10% while unadjusted entropy ranged from 9 to 100%. In addition, under all levels of divergence adjusted entropy never had a false positive rate higher than 9%. Adjusted entropy also identifies important mutations in H1N1pdm PB2 previously identified in the literature that explain changes in divergence between 2008 and 2009 which unadjusted entropy could not identify.

CONCLUSIONS: Based on these results, adjusted entropy provides a reliable and widely applicable host signature identification approach useful for IAV monitoring and vaccine development.

PMID:35962315 | DOI:10.1186/s12859-022-04885-7

Mol Neurobiol. 2022 Aug 12. doi: 10.1007/s12035-022-02969-2. Online ahead of print.

ABSTRACT

Sporadic early-onset Alzheimer’s disease (EOAD) and autosomal dominant Alzheimer’s disease (ADAD) provide the opportunity to investigate the physiopathological mechanisms in the absence of aging, present in late-onset forms. Frontotemporal dementia (FTD) causes early-onset dementia associated to tau or TDP43 protein deposits. A 15% of FTD cases are caused by mutations in C9orf72, GRN, or MAPT genes. Lymphoblastoid cell lines (LCLs) have been proposed as an alternative to brain tissue for studying earlier phases of neurodegenerative diseases. The aim of this study is to investigate the expression profile in EOAD, ADAD, and sporadic and genetic FTD (sFTD and gFTD, respectively), using brain tissue and LCLs. Sixty subjects of the following groups were included: EOAD, ADAD, sFTD, gFTD, and controls. Gene expression was analyzed with Clariom D microarray (Affymetrix). Brain tissue pairwise comparisons revealed six common differentially expressed genes (DEG) for all the patients’ groups compared with controls: RGS20, WIF1, HSPB1, EMP3, S100A11 and GFAP. Common up-regulated biological pathways were identified both in brain and LCLs (including inflammation and glial cell differentiation), while down-regulated pathways were detected mainly in brain tissue (including synaptic signaling, metabolism and mitochondrial dysfunction). CD163, ADAMTS9 and LIN7A gene expression disruption was validated by qPCR in brain tissue and NrCAM in LCLs in their respective group comparisons. In conclusion, our study highlights neuroinflammation, metabolism and synaptic signaling disturbances as common altered pathways in different AD and FTD forms. The use of LCLs might be appropriate for studying early immune system and inflammation, and some neural features in neurodegenerative dementias.

PMID:35962298 | DOI:10.1007/s12035-022-02969-2

J Infect Dis. 2022 Aug 12;226(Supplement_1):S87-S94. doi: 10.1093/infdis/jiac069.

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus infections result in a considerable mortality and morbidity among the aging population globally. Influenza vaccination for older adults before the seasonal influenza epidemic has been evaluated to be cost-effective in many countries. Interventions against RSV in older adults are in the pipeline, and evaluating their cost-effectiveness is crucial for decision making. To inform such evaluations, our aim was to estimate average costs and health-related quality of life (HRQoL) in older adults with RSV and influenza infection.

METHODS: The European RESCEU observational cohort study followed 1040 relatively healthy community-dwelling older adults aged 60 years and older during 2 consecutive winter seasons. Health care resource use and HRQoL were collected and analyzed during RSV episodes, and also during influenza episodes. Country-specific unit cost data were mainly obtained from national databases. Direct costs were estimated from a patient, health care provider, and health care payers’ perspective, whereas indirect costs were estimated from a societal perspective. Due to small sample size, no formal statistical comparisons were made.

RESULTS: Thirty-six RSV and 60 influenza episodes were reported, including 1 hospitalization. Means (median; first-third quartile) of €26.4 (€5.5; 0-47.3) direct and €4.4 (€0; 0-0) indirect costs were reported per nonhospitalized RSV episode, and €42.5 (€36; 3.3-66.7) direct and €32.1 (€0; 0-0) indirect costs per nonhospitalized influenza episode. For RSV episodes, the utility value decreased from 0.896 (0.928; 0.854-0.953) to 0.801 (0.854; 0.712-0.937) from preseason to 1 week after symptom onset; for influenza, the change was from 0.872 (0.895; 0.828-0.953) to 0.664 (0.686; 0.574-0.797).

CONCLUSIONS: The average costs and HRQoL estimates of older adults treated outside the hospital can be used to inform the design of future studies and the decision making regarding interventions to prevent RSV infection in older adults. Larger studies are needed to provide better country-specific and complementary cost estimates and to allow for formal statistical comparison of costs between RSV and influenza.

CLINICAL TRIALS REGISTRATION: NCT03621930.

PMID:35961055 | DOI:10.1093/infdis/jiac069

Aesthet Surg J. 2022 Aug 12:sjac219. doi: 10.1093/asj/sjac219. Online ahead of print.

ABSTRACT

BACKGROUND: Paradoxical adipose hyperplasia (PAH), a rare side effect of CoolSculpting (cryolipolysis), is characterized by fatty enlargement of the treatment area occurring months after the procedure.

OBJECTIVES: The purpose of this study is to report a retrospective case series of patients diagnosed with PAH at our institution, increase the collective understanding of this complication and subsequent management, and raise the question of who should ethically perform cryolipolysis.

METHODS: All participants diagnosed with PAH by a plastic surgeon at a large academic medical center were identified. Demographic information, medical history, procedure details, time to PAH diagnosis, and corrective surgical intervention details were collected. Mean duration of time from cryolipolysis treatment to diagnosis of PAH was calculated, along with other descriptive statistics. A scoping review of all PAH literature published in PubMed, Embase, and Web of Science was also conducted.

RESULTS: Four patients diagnosed with PAH after cryolipolysis were identified for inclusion in this study. The calculated incidence of PAH at our center was 0.67%. All patients requested therapy for PAH and subsequently underwent either liposuction, abdominoplasty, or both. The mean duration of in-person follow-up time after final surgical treatment of PAH was 13.8 ± 19.8 months (range: 2.8-43.5). Fortunately, no patients showed signs of PAH recurrence, and three out of four patients did not show signs of residual deformity.

CONCLUSIONS: Findings from this patient cohort and scoping review provide evidence that although revisions may be required, conventional body contouring methods, not in the armamentarium of non-plastic surgeon practitioners, effectively alleviated PAH.

PMID:35961054 | DOI:10.1093/asj/sjac219

J Travel Med. 2022 Aug 12:taac096. doi: 10.1093/jtm/taac096. Online ahead of print.

NO ABSTRACT

PMID:35961008 | DOI:10.1093/jtm/taac096

J Am Acad Orthop Surg Glob Res Rev. 2022 Aug 12;6(8). doi: 10.5435/JAAOSGlobal-D-22-00125. eCollection 2022 Aug 1.

ABSTRACT

INTRODUCTION: Genicular nerve radiofrequency ablation (GNRFA) is an increasingly used nonsurgical treatment modality for patients with advanced knee osteoarthritis. Previous studies have demonstrated this to be an effective and safe method to decrease pain and increase functionality in this patient population. The purpose of this study was to compare 2-year postoperative complication rates and rates of prolonged postoperative opioid usage between patients undergoing total knee arthroplasty (TKA) after previous GNRFA and those undergoing TKA alone.

METHODS: Patients who underwent primary TKA after prior GNRFA (GNRFA-TKA) of the ipsilateral knee were identified in a national all-payer claims database from 2010 to 2019. Univariate and multivariable analyses were conducted comparing those with prior GNRFA and those without. Outcomes of interest included prolonged postoperative opioid usage, 2-year revision rates, and 90-day medical complications. Statistical analysis was conducted using R software provided by the PearlDiver Database.

RESULTS: In total, 675 patients in the GNRFA-TKA cohort were compared with a control cohort of 255,351 patients. Genicular nerve radiofrequency ablation-total knee arthroplasty patientshad lower odds of prolonged opioid use postoperatively (OR: 0.478; 95%: 0.409 to 0.559; P < 0.001). No notable difference was observed in the 2-year surgical outcomes between cohorts. Patients in the GNRFA-TKA cohort had lower odds of requiring a blood transfusion and having postoperative anemia, all arrhythmias, and urinary infections compared with primary TKA control patients.

CONCLUSION: Preoperative GNRFA leads to a lower rate of prolonged postoperative opioid use in patients undergoing TKA, without an increased risk of complications. Future prospective studies are needed to validate the findings of this database study.

PMID:35960987 | DOI:10.5435/JAAOSGlobal-D-22-00125

Cutis. 2022 Jun;109(6):E36-E38. doi: 10.12788/cutis.0551.

ABSTRACT

Residency is both physically and mentally taxing. Although some tout these struggles as a rite of passage to practice medicine, rates of physician burnout and suicide unfortunately remain higher than the general population. Limitations on work hours, mandatory reporting of work hour violations, and resident wellness programs have aimed to improve these statistics, but the time constraints and physical demands of residency offer little room for trainees to focus on their mental health. In 2020, the COVID-19 pandemic tested an already strained health care system, bringing to light the prevalence of depression and anxiety among residents. This article explores this prevalence and highlights several modalities available to residents who are seeking to prioritize their mental health.

PMID:35960972 | DOI:10.12788/cutis.0551

Hum Vaccin Immunother. 2022 Aug 12:2087412. doi: 10.1080/21645515.2022.2087412. Online ahead of print.

ABSTRACT

This article describes the results of a preclinical safety and immunogenicity study of QazCovid-in®, the first COVID-19 vaccine developed in Kazakhstan, on BALB/c mice, rats, ferrets, Syrian hamsters and rhesus macaques (Macaca mulatta). The study’s safety data suggests that this immunobiological preparation can be technically considered a Class 5 nontoxic vaccine. The series of injections that were made did not produce any adverse effect or any change in the general condition of the model animals’ health, while macroscopy and histology studies identified no changes in the internal organs of the BALB/c mice and rats. This study has demonstrated that a double immunization enhances the growth of antibody titers as assessed by the microneutralization assay (MNA) and the enzyme-linked immunosorbent assay (ELISA) in a pre-clinical immunogenicity test on animal models. The best GMT results were assessed in MNA and ELISA 7 days after re-vaccination; however, we noted that GMT antibody results in ELISA were lower than in MNA. A comparative GMT assessment after the first immunization and the re-immunization identified significant differences between model animal groups and a growth of GMT antibodies in all of them; also, differences between the gender groups were statistically significant. Moreover, the most marked MNA immune response to the QazCovid-in® vaccine was seen in the Syrian hamsters, while their SARS-CoV-2-specific antibody activity as assessed with ELISA was the lowest.

PMID:35960911 | DOI:10.1080/21645515.2022.2087412

J Clin Oncol. 2022 Aug 12:JCO2102815. doi: 10.1200/JCO.21.02815. Online ahead of print.

ABSTRACT

PURPOSE: In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results.

METHODS: Patients with RRMM who had received ≥ 2 prior lines of therapy, with disease refractory to last therapy and either refractory or relapsed and refractory to lenalidomide and a PI were randomly assigned (1:1) to receive EPd or Pd. The primary end point was PFS per investigator assessment. ORR and OS were secondary end points planned to be tested hierarchically.

RESULTS: A total of 117 patients were randomly assigned to EPd (n = 60) and Pd (n = 57). Among treated patients (EPd 60, Pd 55), there were 37 (61.7%) deaths in the EPd group and 41 (74.5%) in the Pd group, most commonly because of disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was significantly improved with EPd (29.8 [22.9 to 45.7] months) versus Pd (17.4 [13.8 to 27.7] months), with a hazard ratio of 0.59 (95% CI, 0.37 to 0.93; P = .0217). OS benefit with EPd was observed in most patient subgroups. The safety profile of EPd was consistent with prior reports with no new safety signals detected.

CONCLUSION: EPd demonstrated a statistically significant improvement in OS versus Pd in patients with RRMM previously treated with lenalidomide and a PI who had disease refractory to last therapy. In this setting, ELOQUENT-3 is the first randomized study of a triplet regimen incorporating a monoclonal antibody and Pd to improve both PFS and OS significantly.

PMID:35960908 | DOI:10.1200/JCO.21.02815